Serum CAPN1 and CLEC2 as Biomarkers for Hearing Loss Severity and Internal Auditory Artery Narrowing in Sudden Sensorineural Hearing Loss.

Background: The pathogenesis of sudden sensorineural hearing loss (SSNHL) remains unclear, with inner ear microcirculatory disturbance being an important mechanism. However, serum biomarkers for evaluating this mechanism are inadequately studied. This study investigated the expression of calpain-1 (CAPN1) and C-type lectin-like receptor 2 (CLEC2) and their correlations with hearing loss severity and inner ear artery diameters in SSNHL patients. Methods: In this prospective study, we consecutively enrolled 150 patients with SSNHL admitted between March 1, 2021, and June 1, 2025, and 150 healthy controls undergoing routine physical examination. Serum CAPN1 and CLEC2 concentrations were measured using enzyme-linked immunosorbent assay (ELISA). Vascular measurements were based on MRI-derived large artery caliber (including the internal auditory artery, basilar artery, and anterior inferior cerebellar artery). Pearson correlation analysis was used to evaluate the relationship between CAPN1, CLEC2 and these arterial diameter parameters. Logistic regression analysis was performed to identify risk factors for SSNHL. Receiver operating characteristic (ROC) curves were used to evaluate the discriminative efficacy of CAPN1 and CLEC2. Results: CAPN1 and CLEC2 levels were significantly elevated in the SSNHL group and increased with the severity of hearing loss (P < 0.001). All three arterial diameters were significantly smaller than those in the healthy group and were negatively correlated with CAPN1 and CLEC2 levels (P < 0.001). Multivariable logistic regression analysis showed that elevated WBC count, neutrophil count, CAPN1, and CLEC2 were independent risk factors, whereas increased arterial diameter was a protective factor (P < 0.05). The AUCs for CAPN1 alone, CLEC2 alone, and both combined were 0.804, 0.793, and 0.863, respectively, demonstrating good discriminative performance. Conclusion: Elevated serum CAPN1 and CLEC2 levels correlated with reduced diameters of arteries supplying the inner ear and severity of hearing loss in patients with SSNHL, suggesting their potential value as novel biomarkers for evaluation of inner ear microcirculatory disturbance and prediction of SSNHL. However, external validation and longitudinal outcome studies are warranted to establish their clinical applicability.